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编号:11258160
Oral Candida Isolates Colonizing or Infecting Human Immunodeficiency Virus-Infected and Healthy Persons in Mexico
     Laboratorio de Micología Medica, Departamento de Inmunología, Microbiología y Parasitología, Facultad de Medicina y Odontología, Universidad del País Vasco-Euskal Herriko Unibertsitatea, Bilbao, Spain

    Facultad de Odontología, Universidad Nacional Autonoma de Mexico, Mexico DF, Mexico

    Laboratorio de Micología Medica, Departamento de Enfermería I, Universidad del País Vasco-Euskal Herriko Unibertsitatea, Bilbao, Spain

    Cátedra de Medicina Bucal, Departamento de Estomatología, Facultad de Medicina y Odontología, Universidad del País Vasco-Euskal Herriko Unibertsitatea, Bilbao, Spain

    Departamento de Epidemiología, Hospital Infantil de Mexico Dr. Federico Gomez, Mexico DF, Mexico

    Department of Medicine, Division of Infectious Diseases, South Texas Centers for Biology in Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas

    ABSTRACT

    Oral yeast carriage was studied in 312 Mexican subjects. Candida albicans was the most frequent species, but other Candida spp. were isolated from 16.5 to 38.5% of patients. Colonization did not correlate with CD4+ number or viral load, but highly active antiretroviral therapy reduced the frequency of candidiasis. Most isolates were susceptible to fluconazole, but 10.8% were resistant to one or more azoles.

    TEXT

    It is estimated that the oral cavity is colonized by Candida in 40 to 60% of persons (39). Oropharyngeal candidiasis is the most prevalent complication in human immunodeficiency virus-infected patients with AIDS (HIV/AIDS) (1, 13, 21). The introduction of highly active antiretroviral therapy (HAART) has reduced the prevalence of opportunistic infections, including candidiasis (5, 7, 11). However, HAART is not worldwide available, and the emergence of antifungal-resistant isolates of Candida albicans has been reported (20).

    In Mexico, most clinical laboratories do not routinely perform antifungal susceptibility testing, and little is known about the antifungal susceptibility profiles of Candida isolates in this country. To elucidate the status of oral Candida carriage and antifungal susceptibility patterns in Mexico, we conducted a 3-year prospective study of 111 adults infected with HIV/AIDS and 201 non-HIV-infected persons at the General Hospital of Mexico, the Federico Gomez Child Hospital, and the Odontology Clinics at the Facultad de Odontología (UNAM) in Mexico DF. Persons were distributed into four groups: 51 HIV/AIDS-infected adults, 109 non-HIV-infected adults, and 60 HIV/AIDS-infected and 92 non-HIV-infected children.

    Data on patient demographics, history of prior mycoses, antifungal treatment, and medications were collected at enrolment. Patients without antifungal treatment in the preceding 6 months were eligible. All patients were subjected to clinical evaluation, including HIV RNA and CD4+ measurements for HIV-infected patients (Tables 1 to 3). Healthy volunteers were selected from persons seeking dental care at the UNAM. Informed consent was obtained from all persons. Approval was obtained from the Human Ethics, Research, and Publications Committee of the UNAM and from the rest of medical institutions involved.

    Swabs were taken from oral lesions when present, the buccal mucosa, the floor of the mouth, and the dorsal surface of the tongue. Swabs were plated onto Sabouraud dextrose agar with chloramphenicol and incubated at 36°C for 2 days (and 7 days at 30°C). Isolates were identified by mycological standard methods (3, 22). Antifungal susceptibility was assessed by Fungitest (Bio-Rad, Paris, France) according to the manufacturer's instructions. C. parapsilosis (ATCC 22019) and C. krusei (ATCC 6258) were used as quality controls. Fungitest has shown high to excellent correlation compared to the NCCLS M-27A method (9, 23-25). However, its qualitative approach could be a main limitation because it does not provide MICs, in contrast to the quantitative M-27A or EUCAST methods. The two-tailed Student t test was used to compare differences between continuous variables, and the chi-square test was used for categorical variables.

    The Mexican National Council of Prevention and Control of AIDS (CONASIDA) reported that 69,795 Mexican persons suffered from AIDS in the period from 1983 to 2003 (8) and more than 200,000 Mexicans were infected by HIV. Little is known about the etiological importance of Candida oral colonization and infection among the Mexican people (12). In the present study (Table 1), 66.7% (74 patients) of HIV/AIDS were colonized or infected by yeasts, and 27% of them (10 patients) were colonized by non-C. albicans species. In addition, 51.7% (104 patients) of persons without HIV infection were also colonized or infected by yeasts, and 42.3% of them (44 patients) were colonized by non-C. albicans species. In both groups, C. glabrata was the most frequent non-C. albicans species. Overall, non-C. albicans species were isolated from 28.7% of persons: C. glabrata from 35 patients (18.7% of all yeast isolates), C. tropicalis from 11 (5.9% of all yeast isolates), Saccharomyces cerevisiae from 3 (1.6% of all yeast isolates), and C. parapsilosis from 2 (1.1% of all yeast isolates). However, neither C. dubliniensis nor C. krusei were isolated from any of the oral specimens. There were nine episodes of infection or colonization by two different yeast species. Non-C. albicans isolates were associated mainly with oral colonization of persons without HIV infection (P < 0.05). This distribution was similar to that observed in other American and European studies (16-18, 26, 27). Overall, yeasts were isolated from 59.9% of the subjects; of these, 32.7% presented with oral lesions by yeasts. This rate coincides with the 31.6% prevalence reported for oral candidiasis in Mexico during the last 12 years in HIV-infected patients (19). Moreover, only 12% of children infected with HIV/AIDS with oral colonization suffered from candidiasis. Most cases of oral candidiasis are caused by C. albicans (63.7% of isolates in the present study); however, the emergence of other species have been reported (2). Moreover, HAART influenced the carriage of Candida spp., reducing the frequency of oral candidiasis. For HIV patients, the status of yeast carrier was not associated with CD4+-cell count or viral load in the present study as has been described by others (1, 5, 11).

    Antifungal resistance to fluconazole (FCZ), itraconazole (ITZ), and ketoconazole (KTZ) has been described and particularly in the setting of oral candidiasis in HIV/AIDS patients (6, 14, 15, 25, 26). Cross-sectional surveys have indicated a prevalence of FCZ-resistant oral C. albicans isolates of 12 to 19% (20). Before the use of HAART, Martins et al. (14, 15) found a prevalence of Candida spp. resistant to FCZ of 22% in North Americans with oral candidiasis and of 14% in asymptomatically colonized patients. After the introduction of HAART, the same cohort showed a declining rate of oral candidiasis and carriage of Candida spp., as well as a trend toward less-frequent in vitro resistance to FCZ. In the present study, 18.7% of isolates were resistant at least to one azole antifungal (KTZ and ITZ were the less active). The majority of resistant isolates were C. glabrata from patients without HIV infection and C. albicans from patients infected with HIV/AIDS. This susceptibility did not differ from previously published data of the American SENTRY program (10, 17). The overall resistance of C. albicans isolates to ITZ was 8.1%. However, nearly one-third of the isolates from patients with HIV/AIDS with candidiasis were intermediate susceptible. Importantly, resistance to FCZ was very low: only 2.8% of isolates from colonized persons were resistant, and all isolates from patients with HIV/AIDS with candidiasis were susceptible. The FCZ-intermediate isolates represented 5.9% of all C. albicans isolates. We did not observe resistance to amphotericin B or 5-fluorocytosine. A lower number of C. glabrata isolates (20%) from Mexican subjects were resistant to ITZ than in the SENTRY program (32.8 to 34.9%) (10, 17). Among the 35 isolates of C. glabrata, 5.7% were resistant to FCZ, a figure similar to that observed in the SENTRY studies (5.7 to 8.7%). C. tropicalis isolates showed a different susceptibility pattern since two of these isolates were resistant (18.2%) to ITZ and one was resistant to FCZ (9.1%). Both isolates of C. parapsilosis were susceptible to ITZ and FCZ. S. cerevisiae was susceptible to all of the antifungals tested (4, 10, 17).

    ACKNOWLEDGMENTS

    L.O.S.-V. was a visiting Scholar at the Universidad del País Vasco from the Programa de Becas MAE Curso 2002-2003 de la Agencia Espaola de Cooperacion Internacional. This study was in part supported by grants from the Universidad del País Vasco-Euskal Herriko Unibertsitatea (project 1/UPV 00093.327-E-14645/2002), from the Fondo de Investigaciones Sanitarias del Ministerio de Sanidad (project PI030662/2003), and PAPIIT 214300 DGAPA-UNAM (Mexico).

    We thank Patricia Perez Ríos, Hilda Hidalgo Loperena, and Javier Romo García for assistance with clinical data from the Department of Stomatology and the Unit of Infectology of the Hospital General de Mexico, Mexico DF, Mexico.

    REFERENCES

    Barchiesi, F., M. Maracci, B. Radi, D. Arzeni, J. Baldassarri, A. Giacometti, and G. Scalise. 2002. Point prevalence, microbiology and fluconazole susceptibility patterns of yeast isolates colonizing the oral cavities of HIV-infected patients in the era of highly active antiretroviral therapy. J. Antimicrob. Chemother. 50:999-1002.

    Barchiesi, F., V. Morbiducci, F. Ancarani, and G. Scalise. 1993. Emergence of oropharyngeal candidiasis caused by non-albicans species of Candida in HIV-infected patients. Eur. J. Epidemiol. 9:455-456.

    Bikandi, J., R. San Millán, M. D. Moragues, G. Cebas, D. C. Coleman, G. Quindos, and J. Ponton. 1998. Rapid identification of Candida dubliniensis by indirect immunofluorescence based on differential localization of antigens on C. dubliniensis blastospores and Candida albicans germ tubes. J. Clin. Microbiol. 36:2428-2433.

    Blignaut, E., S. Messer, R. J. Hollis, and M. A. Pfaller. 2002. Antifungal susceptibility of South African oral yeast isolates from HIV/AIDS patients and healthy individuals. Diagn. Microbiol. Infect. Dis. 44:169-174.

    Ceballos-Salobrea, A., L. Gaitán-Cepeda, L. Ceballos-García, and L. P. Samaranayake. 2004. The effect of antiretroviral therapy on the prevalence of HIV-associated oral candidiasis in a Spanish cohort. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. 97:345-350.

    Ceballos-Salobrea, A., L. A. Gaitán-Cepeda, F. Orihuela-Caada, D. Barrionuevo Olea, L. Ceballos-García, and G. Quindos. 1999. Resistencia in vitro a los antifúngicos en Candida albicans de pacientes infectados por el VIH con y sin candidiasis oral. Rev. Iberoam. Micol. 16:194-197.

    Ceballos-Salobrea, A., G. Quindos-Andres, and L. Ceballos-García. 2000. The influence of different risk behaviors in the appearance of oral candidiasis in AIDS patients. Med. Oral 5:71-80.

    CONASIDA. 2003. Panorama epidemiologico del VIH/SIDA e ITS en Mexico. Consejo Nacional para la Prevencion y control del VIH/SIDA, Secretaría de Salud, Mexico. Direccion General de Epidemiología, Mexico City, Mexico. [Online.] http://www.salud.gob.mx/conasida.

    Davey, K. G., A. D. Holmes, E. M. Johnson, A. Szekely, and D. W. Warnock. 1998. Comparative evaluation of Fungitest and broth microdilution methods for antifungal drug susceptibility testing of Candida species and Cryptococcus neoformans. J. Clin. Microbiol. 36:926-930.

    Diekema, D. J., M. A. Pfaller, S. A. Messer, A. Houston, R. J. Hollis, G. V. Doern, R. N. Jones, et al. 1999. In vitro activities of BMS-207147 against over 600 contemporary clinical bloodstream isolates of Candida species from the SENTRY antimicrobial surveillance program in North America and Latin America. Antimicrob. Agents Chemother. 43:2236-2239.

    Diz-Dios, P., A. Ocampo, I. Otero, I. Iglesias, and C. Martínez. 2001. Changes in oropharyngeal colonization and infection by Candida albicans in human immunodeficiency virus-infected patients. J. Infect. Dis. 183:355-356.

    Gaitan-Cepeda, L., M. Cashat-Cruz, J. J. Morales-Aguirre, L. Sanchez-Vargas, S. Aquino-Garcia, R. Fragoso-Rios, V. Cuairan-Ruidiaz, C. Avila-Figueroa, J. Morales, and C. A. Figueroa. 2002. Prevalence of oral lesions in Mexican children with perinatally acquired HIV: association with immunologic status, viral load, and gender. AIDS Patient Care STDS 16:151-156.

    Gottfredsson, M., G. M. Cox, O. S. Indridason, G. M. D. De Almeida, A. E. Heald, and J. R. Perfect. 1999. Association of plasma levels of human immunodeficiency virus type 1 RNA and oropharyngeal Candida colonization. J. Infect. Dis. 180:534-537.

    Martins, M. D., M. Lozano-Chiu, and J. H. Rex. 1997. Point prevalence of oropharyngeal carriage of fluconazole-resistant Candida in human immunodeficiency virus-infected patients. Clin. Infect. Dis. 25:843-846.

    Martins, M. D., M. Lozano-Chiu, and J. H. Rex. 1998. Declining rates of oropharyngeal candidiasis and carriage of Candida albicans associated with trends toward reduced rates of carriage of fluconazole-resistant C. albicans in human immunodeficiency virus-infected patients. Clin. Infect. Dis. 27:1291-1294.

    Odds, F. C. 1988. Candida and candidiasis, 2nd ed. Bailliere Tindall, London, United Kingdom.

    Pfaller, M. A., R. N. Jones, G. V. Doern, H. S. Sader, R. J. Hollis, S. A. Messer, et al. 1998. International surveillance of bloodstream infections due to Candida species: frequency of occurrence and antifungal susceptibilities of isolates collected in 1997 in the United States, Canada and South America for the SENTRY program. J. Clin. Microbiol. 36:1886-1889.

    Quindos, G., M. T. Ruesga, E. Martín-Mazuelos, R. Salesa, R. Alonso-Vargas, A. J. Carrillo-Muoz, S. Brena, R. San-Millán, and J. Ponton. 2004. In-vitro activity of 5-fluorocytosine against 1,021 Spanish clinical isolates of Candida and other medically important yeasts. Rev. Iberoam. Micol. 21:63-69.

    Ramirez-Amador, V., L. Esquivel-Pedraza, J. Sierra-Madero, G. Anaya-Saavedra, I. Gonzalez-Ramirez, and S. Ponce-de-Leon. 2003. The changing clinical spectrum of human immunodeficiency virus-related oral lesions in 1,000 consecutive patients: a 12-year study in a referral center in Mexico. Medicine 82:39-50.

    Sanglard, D., and F. C. Odds. 2002. Resistance of Candida species to antifungal agents: molecular mechanisms and clinical consequences. Lancet Infect. Dis. 2:73-85.

    Vargas, K. G., and S. Joly. 2002. Carriage frequency, intensity of carriage, and strains of oral yeast species vary in the progression to oral candidiasis in human immunodeficiency virus-positive individuals. J. Clin. Microbiol. 40:341-350.

    Williams, D. W., and M. A. O. Lewis. 2000. Isolation and identification of Candida from the oral cavity. Oral Dis. 6:3-11.

    Willinger, B., P. Apfalter, A. M. Hirschl, A. Makristathis, M. Rotter, and M. Seibold. 2000. Susceptibility testing of Candida species: comparison of NCCLS microdilution method with Fungitest. Diagn. Microbiol. Infect. Dis. 38:11-15.

    Willinger, B., E. Engelmann, H. Hofmann, S. Metzger, P. Apfalter, A. M. Hirschl, A. Makristathis, M. Rotter, B. Raddatz, and M. Seibold. 2002. Multicenter comparison of Fungitest for susceptibility testing of Candida species. Diagn. Microbiol. Infect. Dis. 44:253-257.

    Witthuhn, F., D. Toubas, I. Beguinot, D. Aubert, C. Rouger, G. Remy, and J. M. Pinon. 1999. Evaluation of the Fungitest kit by using strains from human immunodeficiency virus-infected patients: study of azole drug susceptibility. J. Clin. Microbiol. 3:864-866.

    Wroblewska, M. M., E. Swoboda-Kopec, A. Rokosz, E. Krawczyk, H. Marchel, and M. Luczak. 2002. Epidemiology of clinical isolates of Candida albicans and their susceptibility to triazoles. Int. J. Antimicrob. Agents 20:472-475.

    Xu, J., and T. G. Mitchell. 2003. Geographical differences in human oral yeast flora. Clin. Infect. Dis. 36:221-224.(Luis Octavio Sánchez-Varg)